PET100

Summary

PET100 (PET100 cytochrome c oxidase chaperone, HGNC:40038) is a protein-coding gene on chromosome 19p13.2, encoding Protein PET100 homolog, mitochondrial (P0DJ07). Plays an essential role in mitochondrial complex IV maturation and assembly.

Mitochondrial complex IV, or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by this gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 100131801 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +4 more curated relationships
• Clinical variants (ClinVar): 98 total — 3 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 36
• MANE Select transcript: NM_001171155

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40038
Approved symbol	PET100
Name	PET100 cytochrome c oxidase chaperone
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000229833
Ensembl biotype	protein_coding
OMIM	614770
Entrez	100131801

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 TEC

ENST00000456958, ENST00000594797, ENST00000598540, ENST00000600836, ENST00000601406, ENST00000601829, ENST00000623154, ENST00000698396, ENST00000698397, ENST00000698398, ENST00000923270, ENST00000923271, ENST00000923272, ENST00000944473

RefSeq mRNA: 1 — MANE Select: NM_001171155 NM_001171155

CCDS: CCDS54208

Canonical transcript exons

ENST00000594797 — 4 exons

Exon	Start	End
ENSE00003514323	7630823	7630846
ENSE00003973534	7630573	7630659
ENSE00003973538	7631473	7631956
ENSE00003973540	7629793	7629860

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6178 / max 260.2594, expressed in 1812 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173580	23.6178	1812

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	99.27	gold quality
colonic epithelium	UBERON:0000397	98.64	gold quality
monocyte	CL:0000576	98.41	gold quality
leukocyte	CL:0000738	98.22	gold quality
apex of heart	UBERON:0002098	97.60	gold quality
bone marrow	UBERON:0002371	97.42	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.16	gold quality
tonsil	UBERON:0002372	96.81	gold quality
granulocyte	CL:0000094	96.28	gold quality
heart left ventricle	UBERON:0002084	96.16	gold quality
adult mammalian kidney	UBERON:0000082	96.03	gold quality
kidney	UBERON:0002113	96.01	gold quality
primary visual cortex	UBERON:0002436	95.97	gold quality
right atrium auricular region	UBERON:0006631	95.75	gold quality
stromal cell of endometrium	CL:0002255	95.69	gold quality
cortex of kidney	UBERON:0001225	95.62	gold quality
heart	UBERON:0000948	95.57	gold quality
mucosa of transverse colon	UBERON:0004991	95.57	gold quality
ganglionic eminence	UBERON:0004023	95.54	gold quality
skeletal muscle tissue	UBERON:0001134	95.52	gold quality
liver	UBERON:0002107	95.17	gold quality
body of stomach	UBERON:0001161	95.14	gold quality
substantia nigra	UBERON:0002038	95.03	gold quality
temporal lobe	UBERON:0001871	95.02	gold quality
amygdala	UBERON:0001876	95.02	gold quality
lower esophagus mucosa	UBERON:0035834	95.02	gold quality
putamen	UBERON:0001874	94.94	gold quality
islet of Langerhans	UBERON:0000006	94.93	gold quality
pituitary gland	UBERON:0000007	94.83	gold quality
adenohypophysis	UBERON:0002196	94.82	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	19.81
E-HCAD-13	yes	12.96
E-GEOD-100618	no	1207.26

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• COX assembly candidate, ortholog of fungal PET100 (PMID:22356826)
• Protein identified in mammalian mitochondria (PMID:22356826)
• We identify PET100 as a complex IV biogenesis factor in humans and characterize its location and role in mitochondria.We found PET100 (MIM 614770) mutations in ten Lebanese individuals with Leigh syndrome and isolated complex IV deficiency. (PMID:24462369)
• The short isoform of the myofibrillogenesis regulator 1 (MR-1S) as a new COX assembly factor, which works with the highly conserved PET100 and PET117 chaperones to assist COX biogenesis in higher eukaryotes. (PMID:28199844)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pet100	ENSDARG00000098017
mus_musculus	Pet100	ENSMUSG00000087687
rattus_norvegicus	Pet100	ENSRNOG00000050169
drosophila_melanogaster	CG14483	FBGN0034248
caenorhabditis_elegans		WBGENE00013161

Protein

Protein identifiers

Protein PET100 homolog, mitochondrial — P0DJ07 (reviewed: P0DJ07)

All UniProt accessions (7): P0DJ07, A0A0A0MSK2, A0A8V8TLP9, A0A8V8TM67, A0A8V8TN53, M0QZ55, M0R022

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in mitochondrial complex IV maturation and assembly.

Subunit / interactions. Interacts with COX7A2.

Subcellular location. Membrane. Mitochondrion. Mitochondrion inner membrane.

Disease relevance. Mitochondrial complex IV deficiency, nuclear type 12 (MC4DN12) [MIM:619055] An autosomal recessive mitochondrial disorder with onset in early infancy. MC4DN12 features include poor overall growth, metabolic acidosis, profoundly delayed psychomotor development, seizures, hypotonia, and brain abnormalities. Death may occur in the first years of life. Serum lactate and creatine kinase levels are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the PET100 family.

RefSeq proteins (1): NP_001164626* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018625	Pet100	Family

Pfam: PF09803

UniProt features (4 total): transit peptide 1, chain 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DJ07-F1	87.50	0.53

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 128 (showing top): GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, GOCC_MITOCHONDRIAL_ENVELOPE, GOCC_ORGANELLE_INNER_MEMBRANE, SANSOM_APC_TARGETS, chr19p13, GOMF_UNFOLDED_PROTEIN_BINDING, YOSHIMURA_MAPK8_TARGETS_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP, GOCC_ORGANELLE_ENVELOPE, CHICAS_RB1_TARGETS_LOW_SERUM, PECE_MAMMARY_STEM_CELL_UP, ASH1L_TARGET_GENES

GO Biological Process (1): mitochondrial respiratory chain complex IV assembly (GO:0033617)

GO Molecular Function (1): obsolete unfolded protein binding (GO:0051082)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
respiratory chain complex IV assembly	1
mitochondrial respiratory chain complex assembly	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

730 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PET100	PNKD	Q8N490	902
PET100	PET117	Q6UWS5	842
PET100	COX15	Q7KZN9	703
PET100	COX10	Q12887	670
PET100	COX17	Q14061	665
PET100	COX14	Q96I36	661
PET100	COA6	Q5JTJ3	658
PET100	SURF1	Q15526	640
PET100	COX8A	P10176	630
PET100	TACO1	Q9BSH4	629
PET100	SCO1	O75880	624
PET100	COA5	Q86WW8	611
PET100	COX20	Q5RI15	602
PET100	SCO2	O43819	592
PET100	COA3	Q9Y2R0	591

IntAct

0 interactions, top by confidence:

BioGRID (2): PET100 (Negative Genetic), PET100 (Negative Genetic)

ESM2 similar proteins: A0A0B4J2F0, A0A1D8PLP3, A1XQS1, A5E7J0, A5Z2X5, A7TQM5, A8E7D3, B3DFP2, B7Z0X7, C0HK61, C0HK65, C0HLN0, C5DE77, C6Y4A3, E0CX11, E1BHC3, G2TRJ9, L0R6Q1, O13931, O22912, O74433, O94705, P07255, P0DJ07, P0DJE0, P0DKM0, P0DP99, P19173, P20610, P22289, P48505, P81449, P81450, Q02820, Q42841, Q54QR8, Q6BPV1, Q6CCF6, Q6CMH6, Q6CS34

Diamond homologs: A1XQS1, E1BHC3, P0DJ07, P0DJE0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

98 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	27
Likely benign	44
Benign	10

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1458646	NM_001171155.2(PET100):c.1A>T (p.Met1Leu)	Pathogenic
2740392	NM_001171155.2(PET100):c.39C>A (p.Tyr13Ter)	Pathogenic
2848577	NM_001171155.2(PET100):c.66G>A (p.Trp22Ter)	Pathogenic
2698099	NM_001171155.2(PET100):c.115-1G>A	Likely pathogenic
2788135	NM_001171155.2(PET100):c.28-2A>G	Likely pathogenic
2889283	NM_001171155.2(PET100):c.114+1G>A	Likely pathogenic
3584209	NM_001171155.2(PET100):c.3G>A (p.Met1Ile)	Likely pathogenic

SpliceAI

831 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7629767:G:GG	donor_gain	0.9900
19:7630572:GAT:G	acceptor_gain	0.9900
19:7630598:T:TA	acceptor_gain	0.9900
19:7630610:G:A	acceptor_gain	0.9900
19:7630661:T:A	donor_loss	0.9900
19:7630752:A:G	acceptor_gain	0.9900
19:7631471:A:AG	acceptor_gain	0.9900
19:7631472:G:GG	acceptor_gain	0.9900
19:7631807:TCCT:T	acceptor_loss	0.9900
19:7629841:TG:T	donor_gain	0.9800
19:7629859:GG:G	donor_gain	0.9800
19:7629860:GG:G	donor_gain	0.9800
19:7629860:GGT:G	donor_loss	0.9800
19:7629861:G:GC	donor_loss	0.9800
19:7630571:AGAT:A	acceptor_gain	0.9800
19:7630572:GATG:G	acceptor_gain	0.9800
19:7630663:GGCA:G	donor_gain	0.9800
19:7630821:A:AG	acceptor_gain	0.9800
19:7630822:G:GG	acceptor_gain	0.9800
19:7631805:CGTC:C	acceptor_gain	0.9800
19:7629861:G:GG	donor_gain	0.9700
19:7629862:T:G	donor_loss	0.9700
19:7630567:TTCCA:T	acceptor_loss	0.9700
19:7630568:TCCA:T	acceptor_loss	0.9700
19:7630569:CCAGA:C	acceptor_loss	0.9700
19:7630570:CAGA:C	acceptor_loss	0.9700
19:7630571:A:C	acceptor_loss	0.9700
19:7630572:G:A	acceptor_loss	0.9700
19:7630599:G:A	acceptor_gain	0.9700
19:7630755:C:A	acceptor_gain	0.9700

AlphaMissense

483 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:7630606:T:C	F21L	0.988
19:7630608:C:A	F21L	0.988
19:7630608:C:G	F21L	0.988
19:7630633:T:C	F30L	0.972
19:7630635:T:A	F30L	0.972
19:7630635:T:G	F30L	0.972
19:7630591:T:C	F16L	0.968
19:7630593:C:A	F16L	0.968
19:7630593:C:G	F16L	0.968
19:7630607:T:G	F21C	0.968
19:7630595:C:G	P17R	0.967
19:7630607:T:C	F21S	0.966
19:7630595:C:A	P17H	0.965
19:7630601:C:A	A19D	0.961
19:7630634:T:G	F30C	0.961
19:7629849:G:A	E6K	0.958
19:7630594:C:T	P17S	0.946
19:7629850:A:T	E6V	0.943
19:7630574:T:C	M10T	0.943
19:7630586:T:C	L14P	0.942
19:7630592:T:G	F16C	0.938
19:7629859:G:C	R9P	0.936
19:7630586:T:A	L14H	0.933
19:7630613:T:A	V23D	0.930
19:7630575:G:A	M10I	0.929
19:7630575:G:C	M10I	0.929
19:7630575:G:T	M10I	0.929
19:7630634:T:C	F30S	0.928
19:7629851:G:C	E6D	0.915
19:7629851:G:T	E6D	0.915

dbSNP variants (sampled 300 via entrez): RS1001255865 (19:7630096 C>G), RS1001503774 (19:7628944 G>A), RS1001554440 (19:7628678 C>T), RS1001603852 (19:7629831 G>A), RS1002509734 (19:7630086 G>A), RS1002562020 (19:7629760 A>C), RS1002667430 (19:7629212 C>T), RS1002868048 (19:7631300 C>A,G,T), RS1003329572 (19:7631437 C>A,G,T), RS1003505006 (19:7631494 A>C,G), RS1003557616 (19:7631233 C>T), RS1005401216 (19:7628586 G>A), RS1005435959 (19:7629748 T>C), RS1006460160 (19:7629578 C>A,T), RS1007058433 (19:7630978 G>T)

Disease associations

OMIM: gene MIM:614770 | disease phenotypes: MIM:619055

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex IV deficiency, nuclear type 12	Strong	Autosomal recessive
cytochrome-c oxidase deficiency disease	Strong	Autosomal recessive
Leigh syndrome	Moderate	Autosomal recessive
Leigh syndrome with leukodystrophy	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Leigh syndrome	Moderate	AR
mitochondrial disease	Definitive	AR

Mondo (4): mitochondrial complex IV deficiency, nuclear type 12 (MONDO:0033646), Leigh syndrome (MONDO:0009723), (MONDO:0009068), (MONDO:0016815)

Orphanet (0):

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000666	Horizontal nystagmus
HP:0001250	Seizure
HP:0001283	Bulbar palsy
HP:0001290	Generalized hypotonia
HP:0001336	Myoclonus
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001522	Death in infancy
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0001998	Neonatal hypoglycemia
HP:0002133	Status epilepticus
HP:0002151	Increased circulating lactate concentration
HP:0002169	Clonus
HP:0002421	Poor head control
HP:0002490	Increased CSF lactate
HP:0002510	Spastic tetraplegia
HP:0002650	Scoliosis
HP:0003073	Hypoalbuminemia
HP:0003128	Lactic acidosis
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003355	Aminoaciduria
HP:0003593	Infantile onset
HP:0003811	Neonatal death
HP:0003819	Death in childhood
HP:0008151	Prolonged prothrombin time
HP:0008347	Decreased activity of mitochondrial complex IV

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007888	Leigh Disease	C10.228.140.163.100.412; C16.320.565.189.412; C16.320.565.202.810.444; C18.452.132.100.412; C18.452.648.189.412; C18.452.648.202.810.444; C18.452.660.520

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
avobenzone	increases expression	1
chloropicrin	increases expression	1
ICG 001	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

14 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01721733	PHASE2	COMPLETED	Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
NCT02352896	PHASE2	COMPLETED	Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome
NCT03747328	PHASE2	WITHDRAWN	ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
NCT06843811	PHASE2	ENROLLING_BY_INVITATION	Sirolimus for Leigh Syndrome
NCT06990984	PHASE2	NOT_YET_RECRUITING	A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01780168	Not specified	RECRUITING	The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT03137355	Not specified	RECRUITING	The International Registry for Leigh Syndrome
NCT05277363	Not specified	WITHDRAWN	A Study of the Natural Course of SURF1 Deficiency
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT06967831	Not specified	RECRUITING	Drug Repurposing for Mitochondrial Disorders Using iPSCs Derived Neural Cells